Ubiquitin carboxyl-terminal hydrolase 21 (USP21)

Ubiquitin carboxyl-terminal hydrolase 21 (USP21) is a member of the ubiquitin-specific protease (USP) family of deubiquitinating enzymes (DUBs)[3]. It hydrolyzes the isopeptide bond between ubiquitin and target proteins, thus regulating their degradation, localization, and function. USP21 targets a broad spectrum of substrates, including histone H2A (regulating gene transcription)[3][7], the stem cell factor Nanog[6], immune factors such as RIG-I, and viral proteins like HIV-1 Tat[5]. It is involved in diverse physiological processes including cell cycle progression, maintenance of stemness, immune signaling, and cytoskeletal organization[1][4][8]. USP21 is implicated in the progression of multiple cancers and acts as a modulator of cancer cell proliferation, metastasis, and stemness[2]. Research suggests that USP21 may also act as an intrinsic antiviral factor by downregulating the HIV-1 Tat protein and interfering with viral replication[5]. Due to its pivotal role in multiple cell functions and disease states, USP21 is recognized as a promising but challenging therapeutic target.

Other names

Ubiquitin specific peptidase 21Deubiquitinating enzyme 21Ubiquitin-specific-processing protease 21Ubiquitin thioesterase 21Ubiquitin thiolesterase 21PP1490NEDD8-specific protease

Removal of ubiquitin from target proteins (deubiquitination); Modulation of substrate stability (e.g., stabilization of oncogenic or regulatory proteins); Regulation of transcription via histone modification; Interference with viral protein function (e.g., HIV-1 Tat)